Muscle Flashcards
What is the shape of skeletal muscle cells?
Elongated cells containing great number of cytoplasmic filaments
Where does all muscular tissue come from?
Hows does differentiation occur?
Medoserm
Differentiation occurs mainly by a process of cell lengthening and synthesis of myofibrillar proteins
→ Skeletal + Cardiac muscles come from Myotome (paraxial mesoderm)
→ Smooth muscle comes from mesenchymal cells
What are the 3 types of muscular fibers?
- Skeletal Striated muscle fibers
- Cardiac muscle fibers
- Smooth muscle fibers
How do A bands and I bands apprear (dark/pale)?
A bands → dark
I line → pale
What are satellite cells?
Stem cells
- Only in skeletal striated muscle
Between the basement membrane and sarcolemma of striated muscle cells
- Role in tissue repair (normally quiescent, but activated for muscle repair and growth, ex: hypertrophy)
- When needed, extra nuclei can be recruited from satellitle cells by mitotic division → 1 nucleus passing into the sarcoplasm
- Differentiate into myoblasts
What are the characteristics of the nuclei of the different muscle fibers?
Skeletal striated muscle fibers nuclei:
- Multinucleated, in periphery
Cardiac muscle fibers’ nuclei:
- Centrally located nucleus
Smooth muscle fibers’ nuclei:
- Centrally located nucleus → from longitudinal section, looks as wide as the cell
- Cork screw shape
Why are smooth muscle not striated?
No myofibrils, intracellular structure made with actin
What is hypertrophy? Where does it occur?
Increase in muscle fiber size due to synthesis of myofibrils + myoglobin
Occurs only in striated muscles:
- Normal in skeletal muscles
- Abnormal in cardiac muscles (means the heart is not pumping efficiently)
What is Hyperplasia? Where does it occur?
Increase in number of muscle fibers
→ Normal in smooth muscle (uterine wall during pregnancy)
What are the speed of contraction different types of muscles?
Voluntary/Involuntary?
Smooth Muscle: contraction is slow, NOT voluntary control
Striated Skeletal Muscle: contraction is quick/forceful, Voluntary control
Striated Cardiac Muscle: contraction is NOT voluntary, vigorous and rhythmic
What is the role of tendons at both ends of the muscle?
Where are they at the level of the muscle?
Tendon = CT that acts as a mechanical transducer to transfer the forces generated by the contracting muscle cells to the bones
Tendons fuse with the Epimysium (Type I collagen) surrounding the muscle
Tendon = dense regular
Epimysium = dense irregular
What is the structure of a sarcomere?
Delimited by 2 Z-lines
Thin actin filament are attached to Z-lines and go towards the
Thick myosin filaments attached to M-line
Z line - 1/2 I band - 1/2 A band - Peudoband H (with M line) - 1/2 A band - 1/2 I band - Z line
What defines the pseudo band H ?
*inside the A band
It is the section both side of the M-line where the thin filaments don’t reach
If cut a cross section through the H pseudo-band, only see only Thick filaments
How many thick and thin filaments are in each myofibril?
3000 thin filaments
1500 thick filaments
What are the dimensions of muscle fibers?
1-40 mm (length) x 10-100 um (width)
How many myofibrils are in a muscle fiber?
up to 1500 myofibrils (1-2um diameter)
What do you see when you cut a cross section through the A band? I band?
A band → Actin (thin) and Myosin (thick) filaments (darker)
I band → actin filaments only (pale)
What defines the sarcomere?
It is the smallest repetitive subunit of the contratile apparatus
Extends from Z line to Z line (2-3 um)
What protein forms the Z line?
a-actinin → actin filaments bind to it (anchor)
Nebulin → structure to thin filaments
Titin → stability of thick myosin filaments
What are the characteristics of the M line?
- Anchor for the Myosin thick filaments
- Contains Creatin Kinase: P-creatin + ADP → ATP + Creatin
- Myomesin protein crosslinks myosin heavy chains
What are the different components of the thin filaments?
Actin polymer (spheres of 5nm diameter) assemble into a double helix
Tropomyosin are long filaments following the helix shape (2 chained a-helical coiled coil protein)
Troponin:
TnI → Inhibit actin myosin interaction
TnC → Binds Ca2+
TnT → anchors to tropomyosin (Tm binding subunit)
*All 3 subunits are found at each “site”
What can we treat myosin heavy chains to subdivide?
Chymotrypsin → Light meromyosin tail (150.000)+ Heavy meromyosin head (180.000)
Papain → HMMS-2 (60.000) + HMMS-1 (120.000)
*HMMS-1 = ATPase and actin binding site (at the far top of the myosin heavy chains)
During a contraction, what part of the muscle shortens, what part keeps the same length?
Thin and thick filaments don’t change in length
Sarcomere and pseudoband H shorten
How does muscle contraction occur at the molecular level?
*Myosin is like a spring, needs ATP hydrolysis to extended (low energy state is when pulled state)
- Ca binds to Tn → moves tropomyosin away frm myosin head binding site on actin (normally TnI pushed myosin away)
Myosin is bound to ADP + Pi from previous muscle contraction - Myosin binds to actin filaments
- Release of the Pi allows myosin head to come back to “short” configuration (power stroke/release the spring) (also release ADP)
- ATP binds the myosin head → separate myosin head form actin filament
- ATP hydrolyzed to ADP + Pi → pulls the spring (head in extended position)
At the cellular level what structures are responsible for activation of muscle contraction in striated skeletal muscle?
Sarcoplasmic reticulum =
2x Terminal Cisternae connected by connecting tubules (“surrounding” the A band)
T tubules (t / PM / Sarcolemma) → invaginations of the sarcolemma (PM) between 2 adjacent Terminal Cisternae (forms a line between the A and I bands)
Triads = 2 terminal cisterns associated with a central T-tubule segment. The main function of the triads is to translate the action potential from the plasma membrane to the sarcoplasmic reticulum, effecting calcium flow into the cytoplasm and the initiation of muscle contraction.
→ At the level of A-I junction
Calcium ATPase (Calsequestrin) → Ca-binding protein that acts as a buffer in the SR
What happens in the skeleta muscle when an AP is propagated?
- AP is propagated
- Ca2+ is released from SR
- Ca2+ binding to troponin removes blockin action of tropomyosin
- Cross bridges move
- Ca2+ leaves troponin, restores tropomyosin blocking action + Ca2+ is resucked into the SR
REVIEW
What are the 3 coats of connective tissue that organizes skeletal striated muscles?
Epimysium: dense CT surrounding the entire muscle
Perimysium: CT that surrounds each bundle of fibres/fascicles
*No capillaries in epi and peri-
Endomysium: basal lamina + reticular fibers (type III collagen) + elastic fibers
*Capillaries that supply muscle fibers are in the endomysium
*All have reticular fibers + elastic fibers + nerves + fibrocytes
How are red, white and intermediate muscle fibers distinguished?
Based on the amount of oxygen binding protein myoglobin and the mitochondrial content
Fibers are mixed to varying degrees in the same muscle
Red → slow-twitch motor unit, resistant to fatigue
How long is a muscle fiber?
How long is a single sarcomere?
Muscle fiber = 1 - 40 mm (diameter = 10 - 100 um)
Sarcomere = 2-3 um
What is the structure of the sarcoplasmic reticulum of striated skeletal muscle fibers?
2 terminal cisternae at the level of the A-I junctions (close to t-tubules) connected by connective tubule (or tubules of SR)
SR = smooth ER
What are the structural characteristics of thick filaments in skeletal striated muscles?
- ~400 myosin molecules/thick filament
- Each molecule = dimer composed fo 2 tighlty inter winded “heavy chains” → body/tail = L-meromyosin, head = H-meromyosin
- A pair of “light chains” (L1, L2) are associated with each of the 2 globular heads
1 Myosin dimer = 2 heavy chains + 4 light chains
Head contains binding sites for actin, ATP receptor, catalytic site for ATP hydrolysis
- Tails are anchored to the M-line
- Titin (tin elastic filaments) anchor thick filaments to the Z-lines
What are the 3 layers of the wall of the heart?
Epicardium
Myocardium → Thickest part of heart’s wall, made of cardiac muscle fibers
Endocardium → endothelium, CT, smooth muscles (continuous with endothelium of large blood vessels)
What are other names for the neuromuscular junctions?
- Motor-end plate
- Myoneural junction
- Terminal bouton
How is it ensured that contraction occurs synchronously in all muscle fibers?
Muscle fibers are innervated by myelinated nerves in the endomysium through the neuromuscular junction
Myelinated motor nerves branch out within the perimysium and endomysium where each nerve gives rise to several terminal wigs called terminal boutons
*Contraction occurs simultaneously in all sarcomeres, in all myofibrils of one muscle cell, in all muscle cells in a bundle of a muscle
How is influx from neurons used to initiate contraction in muscle?
Neuron’s terminal bouton has synaptic vesicle filled with Ach that fuse to the presynaptic membrane → synaptic cleft → bind to Ach receptors on the postsynaptic membrane
These receptor allow for depolarization of the postsynaptic membrane → depolarizes all the way to the t-tubules (A-I junctions)
In the synaptic cleft, Ach-chlorinesterase cleaves Ach → Acetate + Choline so it detaches from the receptor and is re-internalized in the terminal bouton of the neuron for later release
*Can see mitochondrias in both pre and post synaptic sides
What is the name of the disease caused by the body developping an Ab against Acetyl Choline?
Myastenia Gravis
Where does the basement membrane of the muscle fiber go at the site of neuromuscular junction?
It is continuous with the BM of the Schwann cells/Oligodendrocyte surrounding the axon
What 3 characteristics of the striated cardiac muscle cells confirms that is what we are looking at in a histological slide?
- Intercalated disks
- Centrally located nucleus + cross striations
What are the different junctional complexes found in intercalated disks?
- Between 2 Z-lines/sarcomeres → Fascia (Zonlua) Adherens (Transverse part)
- In between myofibrils →Macula Adherence (Transverse part)
- In lateral parts → gap junctions
What proteins compose the zonula adherens? (between 2 sarcomeres in intercalated disks)
What is the gap?
Intracellualr proteins: a-actinin/vinculin → actin anchoring of terminal web
TM proteins making the junctions: Cadherins
*15nm intercellular space
What proteins compose the macula adherens? (in intercalated disks, at levels of the mitchondrias, not myofibrils)
What is the gap?
Plaque: Desmoplakins I and II, Plakoglobin, Desmocalmin
Intermediate filaments pass through the plate and go back into the cell
TM proteins making the junction: Desmocollin, Desmoglein
*25nm intercellular space
What proteins compose the gap junctions? (in the lateral portion of the intercalated disks)
What is the gap?
6 connexins (CONNEXIN 48 in cardiac muscle) → 1 connexon → 2 coupled connexons form 1 channel (1.5 nm in diameter)
*2nm between both plasma membranes
What is the main structure of the SR in cardiac muscle cells?
Where are t-tubules located?
Not all muscle cells have terminal cisternae, some only have connecting tubules that release Ca2+when t-tubules are depolarized
Some have the triad or a diad, but at the level of the Z-lines
*t-tubules are at the level of the Z-line (unlike skeletal muscles)
What are the particularities of smooth muscle cells?
The shape of the cells?
- Spindle shaped cells (30 - 200 um long) → different diameters depending on where it is cut in the cross section
- Centrally located nucleus
- NO t-tubules, smaller and less organized SR
- Dense bodies
- Irregular arrangement of actin + myosin
- Gap junctions + Zonula Adherens + Desmosomes + Tight junctions
What filaments are found in the sarcoplasm of smooth muscle cells?
Thin filaments → anchored to dense bodies and other en is free in sarcoplasm
- Contain actin and tropomyosin (no troponin)
Dense bodies can be attached at the level of the PM or free in the cytoplasm (NOT the same as hemidesmosomes) → made of a-Actinin like proteins (Z-line?)
Intermediate filaments → anchored to dense patches too
Desmin = component of intermediate filaments in all smooth muscles
Vimentin = component only in vascular smooth muscles
Thick filaments → not attached to dense patches, but parallel to thin filaments
- Made of myosin II
What structure is found on the outside of smooth muscle cells?
What structure is found in the PM?
PM forms caveoles (small invaginations that could act as ‘t-tubules’)
Basement membrane
Reticular Fibers (not called endomysium, just CT)
How does the sliding mechanism / Actin and Myosin interaction occur in smooth muscle cells?
Inactive Myosin state → light chains not phosphorylated: tail of heavy chain is attached to light chains → inhibits binding of the head to actin filaments (no troponin to do so)
Ca2+ → Myosin linght chain kinase → Phosphorylate ligh chains (hydrolysis of ATP) → releases tail → head can bind actin
*Sliding mechanism + actin filaments bound to dense bodies produces slow contractions
Decrease in Ca2+ leels cause inactivation of myosin light-chain kinase → relaxation
What is Calsequestrin?
Calcium ATPase (Calsequestrin) → Ca-binding protein that acts as a buffer in the SR
